There is provided a method for preparing homofarnesol (1), the method comprising the steps of: a) providing homofarnesylnitrile (2); b) reacting homofarnesylnitrile (2) to homofarnesic acid (3); and c) reacting homofarnesic acid (3) to homofarnesol (1),
wherein the configuration of the double bonds in the compounds 1, 2 and 3 is preserved.

There is provided a method for preparing homofarnesol (1), the method comprising the steps of: a) providing homofarnesylnitrile (2); b) reacting homofarnesylnitrile (2) to homofarnesic acid (3); and c) reacting homofarnesic acid (3) to homofarnesol (1),
wherein the configuration of the double bonds in the compounds 1, 2 and 3 is preserved.

This present invention relates to an improved process to prepare prostacyclin derivatives. One embodiment provides for an improved process to convert benzindene triol to treprostinil via salts of treprostinil and to purify treprostinil.

This present invention relates to an improved process to prepare prostacyclin derivatives. One embodiment provides for an improved process to convert benzindene triol to treprostinil via salts of treprostinil and to purify treprostinil.

This present invention relates to an improved process to prepare prostacyclin derivatives. One embodiment provides for an improved process to convert benzindene triol to treprostinil via salts of treprostinil and to purify treprostinil.

Methods of preparing a fenfluramine active pharmaceutical ingredient are provided. Aspects of the method include (a) hydrolyzing a 2-(3-(trifluoromethyl)phenyl)acetonitrile composition to produce a 2-(3-(trifluoromethyl)phenyl)acetic acid composition; (b) reacting the 2-(3-(trifluoromethyl)phenyl)acetic acid composition with acetic anhydride and a catalyst to produce a 1-(3-(trifluoromethyl)phenyl)propan-2-one composition; and

(c) reductively aminating the 1-(3-(trifluoromethyl)phenyl)propan-2-one composition with ethylamine using a borohydride reducing agent to produce a fenfluramine composition. Also provided are compositions and pharmaceutical ingredients prepared according to the subject methods including a pharmaceutically acceptable salt of fenfluramine and having less than 0.2% by weight in total of trifluoromethyl regioisomers.

Methods of preparing a fenfluramine active pharmaceutical ingredient are provided. Aspects of the method include (a) hydrolyzing a 2-(3-(trifluoromethyl)phenyl)acetonitrile composition to produce a 2-(3-(trifluoromethyl)phenyl)acetic acid composition; (b) reacting the 2-(3-(trifluoromethyl)phenyl)acetic acid composition with acetic anhydride and a catalyst to produce a 1-(3-(trifluoromethyl)phenyl)propan-2-one composition; and

(c) reductively aminating the 1-(3-(trifluoromethyl)phenyl)propan-2-one composition with ethylamine using a borohydride reducing agent to produce a fenfluramine composition. Also provided are compositions and pharmaceutical ingredients prepared according to the subject methods including a pharmaceutically acceptable salt of fenfluramine and having less than 0.2% by weight in total of trifluoromethyl regioisomers.

Methods of preparing a fenfluramine active pharmaceutical ingredient are provided. Aspects of the method include (a) hydrolyzing a 2-(3-(trifluoromethyl)phenyl)acetonitrile composition to produce a 2-(3-(trifluoromethyl)phenyl)acetic acid composition; (b) reacting the 2-(3-(trifluoromethyl)phenyl)acetic acid composition with acetic anhydride and a catalyst to produce a 1-(3-(trifluoromethyl)phenyl)propan-2-one composition; and

(c) reductively aminating the 1-(3-(trifluoromethyl)phenyl)propan-2-one composition with ethylamine using a borohydride reducing agent to produce a fenfluramine composition. Also provided are compositions and pharmaceutical ingredients prepared according to the subject methods including a pharmaceutically acceptable salt of fenfluramine and having less than 0.2% by weight in total of trifluoromethyl regioisomers.

Process for the preparation of a compound of Formula (I), the process comprising the reaction of a compound of Formula (II) with malononitrile in the presence of a base and a palladium catalyst, Formula (II) wherein X, Y and Z, independently of each other, represent fluoro, chloro or C.sub.1-4alkyl; and L is a leaving group; with the proviso that 1 or 2 of X and Y are, independently of each other, fluoro or chloro.

##STR00001##

Process for the preparation of a compound of Formula (I), the process comprising the reaction of a compound of Formula (II) with malononitrile in the presence of a base and a palladium catalyst, Formula (II) wherein X, Y and Z, independently of each other, represent fluoro, chloro or C.sub.1-4alkyl; and L is a leaving group; with the proviso that 1 or 2 of X and Y are, independently of each other, fluoro or chloro.

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